Boron neutron capture therapy (BNCT) for the treatment of mammalian tumors (e.g. cancerous tumor cells) is based on the nuclear reaction between thermal neutrons and boron-10 to yield alpha particles and lithium-7 nuclei: ##STR1##
The high linear energy transfer (LET) alpha particles released in this nuclear reaction have a range in tissue of about 10 .mu.m, approximately equal to the diameter of a single cell. Their destructive effect is, therefore, highly localized to boron-loaded tissue. A key requirement of BNCT is the selective delivery of an adequate concentration of boron-10 to tumors (15-30 .mu.g .sup.10 B/g tumor). The lack of boron compounds with the requisite biological properties has been a major limitation for the clinical use of BNCT. Boronated analogues of compounds that are known to localize in various tumors (amino acids, thioruracils, chlorpromazine, nucleosides, antibodies, etc.) have been the focus of compound development in this area. The rationale for the synthesis of boron-containing nucleosides is that such structures would be conserved by rapidly proliferating tumor cells and phosphorylated by cellular kinases to mononucleotides. These may persist "locked-in" within the tumor cell or possibly be converted to the active precursors of nucleic acids, the di- and triphosphate forms.
A recent review article on BNCT can be found in Barth et al., "Boron Neutron Capture Therapy for Cancer--Realities and Prospects", Cancer, Vol. 70, No. 12, Dec. 15, 1992, pp. 2995-3007. Other reviews are Rolf F. Barth, Albert H. Soloway and Ralph G. Fairchild, "Boron Neutron Capture Therapy of Cancer", Cancer Research, Vol. 50, Feb. 15, 1990, pp. 1061-1070, and Rolf F. Barth et al., "Boron Neutron Capture Therapy for Cancer", Scientific American, Vol. 262, No. 10, October 1990, pp. 100-107. In the latest review on pages 3001-3003 the use of BNCT clinically in the treatment of malignant brain tumors and melanoma is described by Yutaka Mishima and his associates, including working with Duroc pigs and injecting a boron compound around a skin-level melanoma, following with exposure to thermal neutrons, and after several months noting that the melanomas began to shrink and eventually disappeared, reported in The Journal of Investigative Dermatology, Vol. 92, No. 5, Supplement, May 1989, 321S-325S. The "Scientific American" review in the paragraph bridging pages 106-107 also reports achieving through BNCT of a cure of primary melanomas on two patients.
The first mentioned review (i.e. Cancer, supra) on pages 2997-2998 lists some current boron compounds either being used or potentially useful as capture agents for BNCT therapy. Included in that listing is a 5-borono-2'-deoxy uridine, which compound contains a single B atom linked to its nucleic acid moiety of the nucleoside.